Overlapping and asymmetric functions of TCR signaling during thymic selection of CD4 and CD8 lineages.

CD4 and CD8 Lineages TCR Signaling during Thymic Selection of Overlapping and Asymmetric Functions of

Commitment of Immature CD4+8+ Thymocytes to the CD4 Lineage Requires CD3 Signaling but Does Not Require Expression of Clonotypic T Cell Receptor (TCR) Chains

As a consequence of positive selection in the thymus, immature CD4(+)8(+) double-positive, [DP] thymocytes selectively terminate synthesis of one coreceptor molecule and, as a result, differentiate into either CD4(+) or CD8(+) T cells. The decision by individual DP thymocytes to terminate synthesis of one or the other coreceptor molecule is referred to as lineage commitment. Previously, we repo...

Overlapping functions of human CD3 and mouse CD3 in T-cell development revealed in a humanized CD3 -deficient mouse

Humans lacking the CD3 subunit of the pre-TCR and TCR complexes exhibit a mild T lymphopenia, but have normal T cells. By contrast, CD3 -deficient mice are almost devoid of mature T cells due to an early block of intrathymic development at the CD4 CD8 double-negative (DN) stage. This suggests that in humans but not in mice, the highly related CD3 chain replaces CD3 during T-cell development. To...

Precommitment of CD4+CD8+ thymocytes to either CD4 or CD8 lineages.

CD4+ and CD8+ mature T cells arise from CD4+CD8+ precursors in the thymus. During this process, cells expressing T-cell receptors (TCRs) reactive with self major histocompatibility complex (MHC) class I or II molecules are positively selected to the CD8 or CD4 lineage, respectively. It is controversial whether lineage commitment of CD4+CD8+ thymocytes is controlled directly by TCR specificity f...

Early molecular events induced by T cell receptor (TCR) signaling in immature CD4+ CD8+ thymocytes: increased synthesis of TCR-alpha protein is an early response to TCR signaling that compensates for TCR-alpha instability, improves TCR assembly, and parallels other indicators of positive selection

Differentiation of immature CD4+ CD8+ thymocytes into mature CD4+ or CD8+ T cells occurs within the thymus and is dependent upon expression of antigen receptor complexes (T cell receptor [TCR]) containing clonotypic alpha/beta proteins. We have recently found that CD4+ CD8+ thymocytes express low levels of surface TCR because of limitations placed on TCR assembly by the instability of nascent T...